The “Interdisciplinary Centre for Clinical Research” (IZKF) Leipzig is a central research institution within the Faculty of Medicine which supports excellence in research. As part of the faculty’s elite programme, IZKF offers research opportunities to over 60 scientists in 35 projects. Since 2004 IZKF Leipzig is financed by the Faculty of Medicine with an annual budget of € 3 mio. The joint aim of both the Faculty of Medicine and IZKF Leipzig is to establish major links between preclinical and clinical research and practice. This aim will be achieved by concentrating on four major research areas and by the establishment of junior research groups.
The objectives of IZKF Leipzig include:
the establishment of a powerful, efficient structure for clinical research encompassing different disciplines (promotion of structural contacts)
the development of an internationally competitive, characteristic research profile (promotion of excellent research) and the promotion of young researchers.
IZKF’s research is focussed on cell-cell and cell-matrix interactions involved in novel aspects of diagnostics and therapy. There are four areas of research:
Department A: Immunology
Department B: Endocrinology
Department C: Neurosciences
Department D: Molecular Oncology
In addition to these departments, there is a central area (Z) located in Reclam Karree, Inselstraße. It houses the core units, which provide researchers with technological and methodological expertise as well as two Junior Research Groups (cell migration, neural plasticity) and the executive board. The services of an independent management office cooperating with the administrations of the university, the faculty and the hospital enable a rapid and effective deployment of research funds.
IZKF Leipzig was founded in 1996 as part of the government initiative “Health Research 2000” by the Federal Ministry of Education and Research (BMBF). It is connected to eight similar institutions throughout Germany (Aachen, Erlangen, Jena, Köln, Münster, Tübingen, Würzburg and Ulm) which are organized under the umbrella of the “Association of Clinical Research Centres” (ACRC).
A Immunology
Coordinator: Prof. Frank Emmrich (Institute of Clinical Immunology and Transfusion Medicine)
During the first two periods of support (1996-2001), the division A project group focussed on the evaluation of pathogenesis mechanisms, the development of novel diagnostic procedures and the evaluation of new therapeutic approaches. In this context, the question of wether a specific “non”reaction of the immune system can be induced without compromising the resistance to infection has gained special significance.
The projects are related both conceptually and methodologically to others within the IZKF, the Medical Faculty and the Faculties of Biosciences, Physics and Chemistry. This is particularly relevant to projects employing NMR techniques (A02, A05, A17), peptide analysis and synthesis (A02, A05, A18) and microarray analysis (A13, A18, A02, A05).
Recent years have seen an increased focus on experimental animal models within the division, culminating in the successful transfer of tolerance induction into animal model using monoclonal antibodies against human cell surface molecules into an animal model. The next step is to involve the transfer of a complete and functional human immune system into a mouse.
Projects
A02
The CD4-molecule as a target of novel immunotherapies for induction of immunological tolerance
Prof. F. Emmrich (Institute of Clinical Immunology and Transfusion Medicine)
A13
Pathophysiological role of interleukin- 6 target genes
Prof. F. Horn (Institute of Clinical Immunology and Transfusion Medicine)
A17
NMR studies of cartilage degradation in rheumatoid arthritis.
Prof. K. Arnold (Institute for Medical Physics and Biophysics)
A19
Interactions of secretoric phospholipase A2 and its products with phagocytes Prof. J. Arnhold (Institute for Medical Physics and Biophysics)
A20
Immunlogic basics for support of autologous regeneration by extracorporal allogenic liver bioreactor
Prof. A. Bader (BBZ,Cell Techniques and Applied Stem Cell Biology)
A21
Role of membrane anchored TNFα in T cell homeostasis in RA
Dr. U. Wagner (Department of Internal Medicine IV)
B Endocrinology
Coordinator: Prof. Torsten Schöneberg (Institute for Biochemistry)
Until recently, the subject of endocrine research has been mainly restricted to measuring hormone levels to explain changes in organ and tissue function. However, it is now very well established that the aberration of endocrine regulation is not only the result of increased or reduced hormone secretion but also the result of alterations in expression and function of receptors and their downstream signalling molecules. Therefore, several projects focussed on the dissection of new signalling pathways. Two main topics were investigated: 1) thyroid function and its regulation ny glycoprotein hormone receptors; 2) the fat tissue as endocrine organ. The IZKF section endocrinology was joined by an IZKF-Young research group (leader Dr. M. Blüher). The focus of this group was also adipocytes function. Over the grant period, studies on receptors and their signalling cascades involved in obesity became central. Based on several joint studies with in the IZKF and the Medical faculty a DFG-granted Clinical research group (leader Prof. M. Stumvoll) was established during the past IZKF period.
Projects
B15
The role of TNF-alpha converting enzyme (TACE) in the generation and regulation of the soluble leptin receptor (sOB-R)
Prof. J. Kratzsch (Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnosis)
B20
Control of thyroid function during iodine deficiency
PD Dr. K. Krohn (Interdisciplinary Centre for Clinical Research Leipzig)
B21
Role of adipocytokines in the pathogenesis of type 2 diabetes
Dr. A. Körner (Children’s Hospital)
B23
Therapeutic inactivation of constitutively active glycoprotein hormone receptors
Prof. T. Schöneberg (Institute of Biochemistry)
C Neurosciences
Coordinator: Prof. Thomas Arendt (Paul-Flechsig-Institute of Brain Research)
The neuroscientific division of IZKF Leipzig consists of 10 projects which are focussed upon two problems in the field of neurodegenerative diseases, viz. Alzheimer's disease and retina degeneration. The work in the projects is aimed at (i) the elucidation of pathogenic mechanisms and cellular signalling chains, in order to develop novel therapeutic approaches, and (ii) the improvement of the diagnostic paradigms of neurodegenerative diseases.
A central role is played by the question of how the mechanisms of cell proliferation are controlled in the diseased central nervous system. On the one hand, this involves testing the hypothesis that the injured neurons in Alzheimer's disease are trying to compensate the functional deficits by regenerative mechanisms (such as the outgrowth of new cell processes) and that these attempts 'unwarrantedly' recruit a set of cellular mechanisms normally triggering mitotic cell division. As differentiated neurons are uncapable of mitosis, further progress on this signalling pathway(s) must cause an insoluble dilemma for the cells which finally die. A novel neuroprotective concept is being developed which involves the ectopic expression of mitotic inhibitors.
On the other hand, pathogenic processes of de-differentiation and cell proliferation are studied in retinal glial cells. These cells normally support the information processing of retinal neurons. However, they remain capable of mitosis even in the adult retina and in the cases of retinal diseases or injuries (unfortunately , also in about 10% of retina-surgical interventions) they begin to proliferate. This growth of cellular masses (“gliosis”) causes retinal detachment and blindness. The research is aimed at blocking these pathogenic events “down-stream”, i.e., at the level of ligand receptors and ion channels. Promising target molecules are ATP receptors and specific K+ channels of high conductance (“big K+ channels”).
Together with a number of other approaches to the characterization of Alzheimer's disease (involving, e.g., the role of the key molecule amyloid precursor protein, and of oxidative stress), several projects lay particular emphasis on the recruitment and sophisticated examination of suitable patients, as this pays the basis for all further research. In this respect, the use of current imaging methods opens up new levels of diagnostic resolution, in particular by means of the intimate integration of histological and high-resolution magnet resonance tomographical techniques.
Projects
C01
Loss of neuronal differentiation control as a pathogenetic mechanism of Alzheimer’s disease: a diagnostic and therapeutic concept
Prof. T. Arendt (Paul-Flechsig-Institute)
C05
Hypoxia and (neo)vascularization of the retina as a model of the CNS
Prof. A. Reichenbach (Paul-Flechsig-Institute)
C07
Mild cognitive impairment and dementia: epidemiology, outcome and risk factors
Prof. M. C. Angermeyer (Department of Psychiatry)
C08
Neurobiology and course of mild cognitive disorders
Prof. H.-J. Gertz (Department of Psychiatry)
C14
Characterization of neuronal P2 receptors during hypoxia and ischemia
Prof. P. Illes (Rudolf-Boehm-Institute)
C17
The role of Munc13-1 in receptor-mediated APP processing
PD Dr. S. Roßner (Paul-Flechsig-Institute)
C20
Establishing new therapeutic strategies in human in vitro model of ischaemia Prof. C. Allgaier (Rudolf-Boehm-Institute)
C21
Mechanisms of microglia activation during retinal degeneration: roles of MAPK and purinergic P2 receptors
PD Dr. A. Bringmann (Department of Ophthalmology)
C23
Physiological and pathophysiological role of endothelins in the control of glial glutamate transport
Prof. J. Engele (Institute of Anatomy)
C24
Abnormal tau protein phophorylation in neurodegenerative diseases conveys signal transduction
Dr. M. Holzer (Paul-Flechsig-Institute)
C27
The relevance of nicotinergic acetylcholine receptors (nAChR) for the pathophysiology of Parkinsons disease
Prof. J. Schwarz (Department of Neurology)
C29
Mechanisms underlying the enhanced vulnerability of cholinergic neurons in Alzheimer’s disease
Prof. R. Schliebs (Paul-Flechsig-Institute)
D Molecular Oncology
Coordinator: Prof. K. Engeland (Department of Internal Medicine II)
The IZKF Division of Molecular Oncology aims to encourage and formalise close links between innovative tumour diagnostics, tumour therapy and basic research activities. Accordingly, the projects concerned apply molecular biological approaches to issues of direct clinical relevance. The research areas reflect the developing profile of the University Hospital with an emphasis on gastroenterology / hepatology (Projects D01 and D02), gynaecology / oncology (D03) and haematology / oncology (D05).
Each of the projects employs molecular and cell biological techniques to a variety of issues ranging from morphological studies to transcription- and proteome analysis. In addition to the use of common techniques within the D projects, the establishment of a central tissue bank provides common access to tumour material. In this way, each of the projects can benefit from tumour samples (DNA- mRNA- and/or protein) which have been prepared under optimal conditions and documented in a manner consistent with the current regulations. A micro dissection unit suitable for single cell analysis has been integrated into this facility.
Projects
D01
Gene- and Protein expression- profiling of multiple simultaneous hepatocellular carcinomas
Prof. A. Tannapfel (Institute of Pathology)
D02
E2F and the cell cycle regulation in cells of the digestive system
Prof. K. Engeland (Department of Internal Medicine II)
D06
The involvement of CD97 in the Wnt-Signal transduction pathway during colorectal carcinoma development
Prof. G. Aust (Institute of Anatomy)
D07
The role of activation of ß-catenin for the expression of glutamine synthetase in hepatocellular and colorectal carcinomas
Prof. R. Gebhardt (Institute of Biochemistry)
D08
Identification of HLA class I restricted minor histocompatibility antigens and tumor specific antigens in leukemia patients using cDNA expression cloning
Prof. D. Niederwieser (Department of Internal Medicine II)
Z Central Project Groups
Coordinator: PD Dr. Knut Krohn, (IZKF Leipzig)
In addition to the three Junior Research Groups, whose activities augment the IZKF Leipzig Research Divisions, the Central Project Groups include a number of service groups which concentrate on special current methods of medical research and provide general support to the Faculty’s research teams.
The Central Division encompasses the manager’s office, one cross-disciplinary group, three independent research groups fou core units. The core units make advanced methods and applications available to researchers throughout the medical faculty and in the university as a whole.
The main aims of the central division include the provision of internal administrative and technical support on the one hand, and the fostering of interdisciplinarity and collaboration on the other. We have found these objectives to be best served by the grouping and coordination of the management, technical support and research groups into a single organisation.
The manager’s office is our HQ, maintaining smooth lines of communication between the administration of the Universitätsklinikum, the medical faculty and the principle researchers, and taking responsibility for much of the routine administration.
The two independent research groups form a concentration of complementary research interests intended to maintain the perspectives of the major Research Divisions through the establishment of new initiatives.
The centralisation of technologically demanding methodology and expensive equipment in the core units allows us to provide all research projects with access to state-of-the-art research techniques (such as microarray analysis, FACS analysis, cell sorting, DNA sequencing and confocal microscopy) which are performed both reliably and economically to the highest standards. This arrangement does not simply save time and money, it also encourages synergy and interdisciplinarity between groups which employ related methodologies.
Projects
N04
Zellmigration
Dr. W. H. Ziegler (Interdisziplinäres Zentrum für Klinische Forschung Leipzig)
N03
Neural Plasticity
Dr. J. Hirrlinger (Interdisciplinary Centre for Clinical Research Leipzig)
Z01
Management
C. Borchers (Interdisciplinary Centre for Clinical Research Leipzig)
Z03
Core Unit – DNA Technologies
PD Dr. K. Krohn (Interdisciplinary Centre for Clinical Research Leipzig)
Z04
Core Unit – Peptide Technologies
Dr. S. Rothemund (Interdisciplinary Centre for Clinical Research Leipzig)
Z10
Core Unit Fluorescence Technologies
PD Dr. U. Sack (Institute of Clinical Immunology and Transfusion Medicine)
Z17
Core Unit Signalling Technologies
Dr. T. Hermsdorf (Institute of Biochemistry)
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